Adenosine A3 receptor antagonists for treating aging skin and wounds

Abstract

The invention provides a method of improving the appearance of aging skin by administering locally to an area of the aging skin of a subject a cosmetic or dermatological composition that includes an effective amount of an adensoine A3 receptor antagonist and a dermatologically acceptable carrier, thereby improving the appearance of the area of the aging skin.

What is claimed is: 
     
       1. A method of promoting expression of collagen in aging or damaged skin comprising administering locally to an area of the aging or damaged skin of a subject a composition comprising an effective amount of an adenosine A3 receptor antagonist and an acceptable carrier, wherein the adenosine A3 receptor antagonist is selected from the group consisting of 3-propyl-6-ethyl-5 [(ethylthio) carbonyl]-2-phenyl-4-propyl-3-pyridine carboxylate (MRS-1523); 1,4-dihydro-2-methyl-6-phenyl-4-(phenylethynyl)-3,5-pyridinedicarboxylic acid 3-ethyl-5-[(3-nitrophenyl) methyl] ester (MRS-1334); 3-ethyl-5-benzyl-2-methyl-4-phenylethynyl-6-phenyl-1,4-(±)-dihydropyridine-3,5 dicarboxylate (MRS-1191); and 3-ethyl-5-benzyl-2-methyl-6-phenyl-4-styryl-1,4-(±)-dihydropyridine-3,5-dicarboxylate (MRS-1097), thereby promoting the expression of collagen in the area of said aging or damaged skin, wherein the promotion of expression of collagen in said aging or damaged skin improves the appearance of the aging or damaged skin in the areas where the composition is administered. 
     
     
       2. A method for treating damaged skin of a chronic wound site of a subject comprising administering locally to the chronic wound site a composition comprising an effective amount of an adenosine A3 receptor antagonist and an acceptable carrier, thereby promoting the expression of collagen in the damaged skin to treat the chronic wound;
 wherein the adenosine A3 receptor antagonist is selected from the group consisting of 3-propyl-6-ethyl-5[(ethylthio) carbonyl]-2-phenyl-4-propyl-3-pyridine carboxylate (MRS-1523); 1,4-dihydro-2-methyl-6-phenyl-4-(phenylethynyl)-3,5-pyridinedicarboxylic acid 3-ethyl-5-[3-nitrophenyl) methyl] ester (MRS-1334); 3-ethyl-5-benzyl-2-methyl-4-phenylethynyl-6-phenyl-1,4-(*)-dihydropyridine-3,5 dicarboxylate (MRS-1191); and 3-ethyl-5-benzyl-2-methyl-6-phenyl-4-styryl-1,4-(*)-dihydropyridine-3,5-dicarboxylate (MRS-1097); and 
 wherein the chronic wound is selected from the group consisting of a diabetic ulcer, a venous stasis ulcer, an arterial insufficiency ulcer, a pressure ulcer, a chronic post-operative wound, and a chronic post trauma wound. 
 
     
     
       3. The method according to  claim 2 , wherein the pharmaceutical composition is in the form selected from the group consisting of a solution, emulsion, nano emulsion, suspension, microparticles, ointment, cream, lotion, paste, gel, hydrogel, spray, powder, stick, and a patch. 
     
     
       4. The method according to  claim 2 , wherein the pharmaceutical composition is administered topically. 
     
     
       5. The method according to  claim 1 , wherein the skin is aging facial skin, neck skin, or a combination thereof. 
     
     
       6. The method according to  claim 1 , wherein the skin is aging skin selected from the group consisting of wrinkled skin, wizened skin, slaggy skin, thinned skin, and any combination thereof. 
     
     
       7. The method according to  claim 6 , wherein the wrinkled skin is selected from the group consisting of skin comprising wrinkles, skin comprising fine lines, skin comprising coarse deep lines, and any combination thereof. 
     
     
       8. The method according to  claim 1 , wherein the adenosine A3 receptor antagonist is 3-propyl-6-ethyl-5 [(ethylthio) carbonyl]-2-phenyl-4-propyl-3-pyridine carboxylate (MRS-1523). 
     
     
       9. The method according to  claim 2 , wherein the adenosine A3 receptor antagonist is 3-propyl-6-ethyl-5 [(ethylthio) carbonyl]-2-phenyl-4-propyl-3-pyridine carboxylate (MRS-1523). 
     
     
       10. The method according to  claim 1 , wherein the adenosine A3 receptor antagonist is administered in a cosmetic or dermatological composition that further comprises one or more excipients selected from the group consisting of emulsifying agents, pH buffering agents, preservatives, chelating agents, tonicity agents, humectants, antioxidants, and gelling agents. 
     
     
       11. The method according to  claim 10 , wherein the cosmetic or dermatological composition is in the form selected from the group consisting of a solution, emulsion, nanoemulsion, suspension, microparticles, ointment, cream, lotion, paste, gel, hydrogel, spray, powder, stick, and a patch. 
     
     
       12. The method according to  claim 10 , wherein the cosmetic or dermatological composition is administered topically. 
     
     
       13. The method according to  claim 10 , wherein the cosmetic or dermatological composition is administered by injection. 
     
     
       14. The method according to  claim 13 , wherein the injection is intraepidermal injection, intradermal injection, subcutaneous injection, micro-injection, or any combination thereof.